Arylalkylamines are a novel class of positive allosteric modulators at GABA B receptors in rat neocortex

Arylalkylamines are a novel class of positive allosteric modulators at GABA B receptors in rat... Using grease-gap recording from rat neocortical slices, the γ-aminobutyric acid B (GABA B ) receptor agonists baclofen (3–100 μM) and SKF 97541 (3-aminopropyl-methylphosphinic acid) (1–30 μM) elicited reversible and concentration-dependent hyperpolarizing responses, with EC 50 values of 10 and 3 μM, respectively. The hyperpolarizations were antagonised by the GABA B receptor antagonist Sch 50911 ((+)-( S )-5,5-dimethylmorpholinyl-2-acetic acid) (1, 5 and 10 μM). Fendiline ( N -(3,3-diphenylpropyl)-α-methylbenzylamine) (5–50 μM) and its congeners, prenylamine ( N -(3,3-diphenylpropyl)-α-methylphenylethylamine) (10–100 μM) and F551 ( N -(3,3-diphenylpropyl)-α-methyl-3-methoxybenzylamine) (1–30 μM) reversibly enhanced hyperpolarizing responses to the agonists; such effects were reduced by Sch 50911. These arylalkylamines produced leftward shifts of the concentration–response curves, with a marked increase in the maximal hyperpolarization obtained, compared with the agonists alone, F551 being the most potent. These findings suggest that these arylalkylamines represent a new class of positive modulators of GABA B receptor-mediated function. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Pharmacology Elsevier

Arylalkylamines are a novel class of positive allosteric modulators at GABA B receptors in rat neocortex

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Publisher
Elsevier
Copyright
Copyright © 2002 Elsevier Science B.V.
ISSN
0014-2999
DOI
10.1016/S0014-2999(02)02195-7
Publisher site
See Article on Publisher Site

Abstract

Using grease-gap recording from rat neocortical slices, the γ-aminobutyric acid B (GABA B ) receptor agonists baclofen (3–100 μM) and SKF 97541 (3-aminopropyl-methylphosphinic acid) (1–30 μM) elicited reversible and concentration-dependent hyperpolarizing responses, with EC 50 values of 10 and 3 μM, respectively. The hyperpolarizations were antagonised by the GABA B receptor antagonist Sch 50911 ((+)-( S )-5,5-dimethylmorpholinyl-2-acetic acid) (1, 5 and 10 μM). Fendiline ( N -(3,3-diphenylpropyl)-α-methylbenzylamine) (5–50 μM) and its congeners, prenylamine ( N -(3,3-diphenylpropyl)-α-methylphenylethylamine) (10–100 μM) and F551 ( N -(3,3-diphenylpropyl)-α-methyl-3-methoxybenzylamine) (1–30 μM) reversibly enhanced hyperpolarizing responses to the agonists; such effects were reduced by Sch 50911. These arylalkylamines produced leftward shifts of the concentration–response curves, with a marked increase in the maximal hyperpolarization obtained, compared with the agonists alone, F551 being the most potent. These findings suggest that these arylalkylamines represent a new class of positive modulators of GABA B receptor-mediated function.

Journal

European Journal of PharmacologyElsevier

Published: Sep 6, 2002

References

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